Glucagon like peptide-1 (glp-1) in myocardial ischaemia-reperfusion injury.

Glucagon-Like Peptide-1 (GLP-1) is an incretin hormone released by enteroendocrine cells lining the intestine in response to the presence of nutrients. GLP-1 is known to cause increased secretion of insulin from the pancreas and has been identified as one of the crucial components of insulin and in turn glucose homeostasis. GLP-1 has a very short half life of 1-2 minutes, being rapidly degraded by a ubiquitous enzyme called dipeptidyl dipeptidase IV and also undergoing renal excretion. Interestingly GLP-1 mRNA transcripts have been identified in several organs outside of the expected enteropancreatic axis including the heart. Insulin has been shown to reduce cell death in the ischemic-reperfused rat myocardium and in isolated rat myocytes via its ability to activate prosurvival kinase signalling pathways. We propose that GLP-1 could protect the myocardium against ischaemia-reperfusion injury by activating similar prosurvival signalling pathways. Both in-vivo (open chest) and in-vitro (Langendorff perfused) rat heart models of regional ischaemia and reperfusion were used. In-vivo treatment with GLP-1 produced a significant reduction in infarction (% infarct/risk zone) compared to valine pyrrolidide (VP), (an inhibitor of the enzyme dipeptidyl peptidase), and control groups (20.0 2.8, vs. 47.3 4.3, and 44.3 2.4, respectively PO.001). In isolated perfused hearts (where there is no circulating insulin) GLP-1 significantly reduced infarct size compared to VP and control (26.7 2.7 vs. 52.6 4.7 and 58.7 4.1, PO.001) groups respectively. Protection was abolished in the presence of the PI3kinase inhibitor, LY294002 (58.6 4.1), the ERK 1/2 MAPK inhibitor, U0126 (48.3 8.6), the p70s6K inhibitor, Rapamycin (57.1 4.9%) and by the GLP-1 receptor antagonist exendin-9-39 (57.3 3.8). GLP-1 protects the myocardium against ischaemic - reperfusion injury when given throughout ischaemia - reperfusion or when given just five minutes prior to the onset of reperfusion or as a preconditioning mimetic. To further elucidate the mechanism of GLP-1 mediated myocardial preservation we carried out Western blot studies examining the phosphorylation of components of the RISK pathway which showed an increase in the phosphorylation of BAD. The increased phosphorylation of the pro-death peptide BAD, confirmed the potential anti- apoptotic effect of GLP-1. In conclusion we have demonstrated for the first time that GLP-1 protects the rat myocardium against ischaemia-reperfusion injury, both in vivo and in vitro. GLP-1 appears to protect via the up regulation of specific prosurvival kinase pathways. This may represent a new therapeutic potential for this class of drugs currently undergoing trials in the treatment of non-insulin dependent diabetes

Sum Uncertainty Relation in Quantum Theory

We prove a new sum uncertainty relation in quantum theory which states that the uncertainty in the sum of two or more observables is always less than or equal to the sum of the uncertainties in corresponding observables. This shows that the quantum mechanical uncertainty in any observable is a convex function. We prove that if we have a finite number $N$ of identically prepared quantum systems, then a joint measurement of any observable gives an error $\sqrt N$ less than that of the individual measurements. This has application in quantum metrology that aims to give better precision in the parameter estimation. Furthermore, this proves that a quantum system evolves slowly under the action of a sum Hamiltonian than the sum of individuals, even if they are non-commuting.Comment: LaTeX file, no figure, 4 page

Numerical Analysis of Laminar Natural Convection in a Quadrantal Cavity with a Solid Adiabatic Fin Attached to the Hot Vertical Wall

Numerical analysis of laminar natural convection in a quadrantal cavity filled with water having finned hot and cold on adjacent walls have been made to examine heat and fluid flow. Numerical solutions are obtained using a commercial computational fluid dynamics package, FLUENT, using the finite volume method. Effects of the Rayleigh number, Ra, non-dimensional fin location and non-dimensional fin length on the Nusselt number, Nu, as well as stream function and temperature fields are investigated for the range of Ra from 104 to 107

FNR-mediated regulation of bioluminescence and anaerobic respiration in the light-organ symbiont Vibrio fischeri

Vibrio fischeri induces both anaerobic respiration and bioluminescence during symbiotic infection. In many bacteria, the oxygen-sensitive regulator FNR activates anaerobic respiration, and a preliminary study using the light-generating lux genes from V. fischeri MJ1 cloned in Escherichia coli suggested that FNR stimulates bioluminescence. To test for FNR-mediated regulation of bioluminescence and anaerobic respiration in V. fischeri, we generated fnr mutants of V. fischeri strains MJ1 and ES114. In both strains, FNR was required for normal fumarate- and nitrate-dependent respiration. However, contrary to the report in transgenic E. coli, FNR mediated the repression of lux. ArcA represses bioluminescence, and ParcA-lacZ reporters showed reduced expression in fnr mutants, suggesting a possible indirect effect of FNR on bioluminescence via arcA. Finally, the fnr mutant of ES114 was not impaired in colonization of its host squid, Euprymna scolopes. This study extends the characterization of FNR to the Vibrionaceae and underscores the importance of studying lux regulation in its native background

Motion of Bound Domain Walls in a Spin Ladder

The elementary excitation spectrum of the spin-$\frac{1}{2}$ antiferromagnetic (AFM) Heisenberg chain is described in terms of a pair of freely propagating spinons. In the case of the Ising-like Heisenberg Hamiltonian spinons can be interpreted as domain walls (DWs) separating degenerate ground states. In dimension $d>1$, the issue of spinons as elementary excitations is still unsettled. In this paper, we study two spin-$\frac{1}{2}$ AFM ladder models in which the individual chains are described by the Ising-like Heisenberg Hamiltonian. The rung exchange interactions are assumed to be pure Ising-type in one case and Ising-like Heisenberg in the other. Using the low-energy effective Hamiltonian approach in a perturbative formulation, we show that the spinons are coupled in bound pairs. In the first model, the bound pairs are delocalized due to a four-spin ring exchange term in the effective Hamiltonian. The appropriate dynamic structure factor is calculated and the associated lineshape is found to be almost symmetric in contrast to the 1d case. In the case of the second model, the bound pair of spinons lowers its kinetic energy by propagating between chains. The results obtained are consistent with recent theoretical studies and experimental observations on ladder-like materials.Comment: 12 pages, 7 figure

An arbitrated quantum signature scheme

The general principle for a quantum signature scheme is proposed and investigated based on ideas from classical signature schemes and quantum cryptography. The suggested algorithm is implemented by a symmetrical quantum key cryptosystem and Greenberger-Horne-Zeilinger (GHZ) triplet states and relies on the availability of an arbitrator. We can guarantee the unconditional security of the algorithm, mostly due to the correlation of the GHZ triplet states and the use of quantum one-time pads.Comment: 10 pages, no figures. Phys. Rev. A 65, (In press

Engineering Entanglement between two cavity modes

We present scheme for generation of entanglement between different modes of radiation field inside high-Q superconducting cavities. Our scheme is based on the interaction of a three-level atom with the cavity field for pre-calculated interaction times with each mode. This work enables us to generate complete set of Bell basis states and GHZ state

Macroscopic entanglement jumps in model spin systems

In this paper, we consider some frustrated spin models for which the ground states are known exactly. The concurrence, a measure of the amount of entanglement can be calculated exactly for entangled spin pairs. Quantum phase transitions involving macroscopic magnetization changes at critical values of the magnetic field are accompanied by macroscopic jumps in the (T=0) entanglement. A specific example is given in which magnetization plateaus give rise to a plateau structure in the amount of entanglement associated with nearest-neighbour bonds. We further show that macroscopic entanglement changes can occur in quantum phase transitions brought about by the tuning of exchange interaction strengths.Comment: 11 pages, 4 figures, Latex, communicated to Phys. Rev.

Magnetization of coupled spin clusters in Ladder Geometry

In this paper, we construct a class of spin-1/2 antiferromagnetic (AFM) two-chain ladder models consisting of blocks of n-spin tetrahedral clusters alternating with two-spin rungs. For n=4 and 6 and in extended parameter regimes, the exact ground state of the ladder is shown to be a product of the ground states of the rungs and the n-spin blocks, in both zero and finite magnetic fields. In the latter case, magnetization/site (m) versus magenetic field (h) plot exhibits well-defined magnetization plateaus.Comment: 9 pages, latex, 6 figures, To be published in Phys. Rev.

Contribution of rapid evolution of the luxR-luxI intergenic region to the diverse bioluminescence outputs of Vibrio fischeri strains isolated from different environments

Vibrio fischeri serves as a valuable model of bacterial bioluminescence, its regulation, and its functional significance. Light output varies more than 10,000-fold in wild-type isolates from different environments, yet dim and bright strains have similar organization of the light-producing lux genes, with the activator-encoding luxR divergently transcribed from luxICDABEG. By comparing the genomes of bright strain MJ11 and the dimmer ES114, we found that the lux region has diverged more than most shared orthologs, including those flanking lux. Divergence was particularly high in the intergenic sequence between luxR and luxI. Analysis of the intergenic lux region from 18 V. fischeri strains revealed that, with one exception, sequence divergence essentially mirrored strain phylogeny but with relatively high substitution rates. The bases conserved among intergenic luxR-luxI sequences included binding sites for known regulators, such as LuxR and ArcA, and bases of unknown significance, including a striking palindromic repeat. By using this collection of diverse luxR-luxI regions, we found that expression of PluxI-lacZ but not PluxR-lacZ transcriptional reporters correlated with the luminescence output of the strains from which the promoters originated. We also found that exchange of a small stretch of the luxI-luxR intergenic region between two strains largely reversed their relative brightness. Our results show that the luxR-luxI intergenic region contributes significantly to the variable luminescence output among V. fischeri strains isolated from different environments, although other elements of strain backgrounds also contribute. Moreover, the lux system appears to have evolved relatively rapidly, suggesting unknown environment-specific selective pressures